Serotonin, lysergic acid diethylamide, mescaline, bufotenine and harmine were shown by the principal investigator to affect neuromuscular activity and metabolism of the liver fluke, Fasciolo hepatica. There is a high degree of correlation between the psychomimetic potencies of lysergic acid derivatives in man and their neuromuscular effects in the flukes. The basic philosophy of this project is that the more we know about the biochemical effects of these agents in systems lower than mammals, such as the liver fluke, the better will be our chance to understand the effects of these agents in the more complicated organ, the brain of humans. Our basic approach is to study the interaction of psychopharmacological agents with 5-HT receptors in the liver fluke and to compare their effects with homologous systems in the mammalian brain or other tissues. We plan to study the mechanism of activation of adenylate cyclase in the fluke by serotonin, LSD and other agents and to isolate and purify the catalytic and the "hormonal" components of the system. We intend to isolate the LSD-serotonin receptor(s) from the flukes, to study the nature of binding of serotonin, LSD and other psychopharmocological agents to these receptors. We intend to study the physio-chemical properties of the receptors and their interaction with adenylate cyclase through GTP. The role of guanylyl nucleotides and their derivatives on serotonin and LSD effects will be examined. The phosphorylating system that is activated by serotonin will be studied. The nature of the natural protein substrate(s) that are phosphorylated and their role in mediating the physiological effects of LSD and serotonin will be investigated. The novel approach in the project is the use of the LSD-5-HT stimulated adenylate cyclase system in the flukes to study the biochemical and molecular effects of psychopharmacological agents.